This study will examine the functional interaction between the effects of morphine on the spinal and supraspinal structures which determines the degree of analgesia that will be elicited by narcotics administered systemically. Supraspinal and spinal narcotic sensitive mechanisms have been implicated in the mediation of the analgetic effect of systemically administered morphine. However, the available literature regarding the respective roles of these two substrates of action leads to the paradoxical conclusion that each substrate mediates most, or possibly all, of the analgetic effect occasioned by the systemic administration of morphine. Two major experimental approaches using rats as experimental subjects will be used to examine the interactive mode and individual contributions of the two substrates to analgesia. In the first procedure, dose response curves for the analgetic effect of systemically injected morphine in the presence of increasing concentrations of naloxone administered intraventricularly or intrathecally will be generated. In the second procedure, dose response relationships describing the analgesia produced by concurrent intraventricular and intrathecal injections of selected doses of morphine will be constructed. Both procedures permit experimental manipulation of the level of narcotic agonism at the two sites of action. An analysis of either set of dose response curves should reveal the mathematical nature of the spinal-supraspinal interaction which controls analgesia produced by systemic dosage. Further, the latter method produces data which can be displayed in isobolographic format, thus permitting ready visualization of the interactive mode, which, on the basis of preliminary data, is believed to be a hyperbolic function.